Research Article
EQD2 and Overall Treatment Time in the High Dose Rate Brachytherapy of the Advanced Nasopharyngeal Carcinoma B. Arunkumar Sharma1, L. Jaichand Singh1, Ph. Jayshree2, Gaurav Goswami1, Y. Indibor Singh1, Th. Tomcha Singh1 1
Department of Radiotherapy, RCC, RIMS, Imphal 795004, India;
2
Department of Physiology, RIMS, Imphal 795004, India.
Corresponding author: B. Arunkumar Sharma. Email：
[email protected]
Citation: Sharma BA, Singh LJ, Jayshree Ph, Goswami G, Singh YI, Singh TT. EQD2 and Overall Treatment Time in the High Dose Rate Brachytherapy of the Advanced Nasopharyngeal Carcinoma[J]. J Nasopharyng Carcinoma, 2016, 3(5), e33. doi: 10.15383/jnpc.33. Competing interests: The authors have declared that no competing interests exist. Conflict of interest: None. Copyright:
2016 By the Editorial Department of Journal of Nasopharyngeal Carcinoma. This is an open-
access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract: The aim of this study is to evaluate the decrease of EQD2 (biologically equivalent dose in 2 Gy fraction) and its correlation with local control of tumour in the treatment of the advanced nasopharyngeal carcinoma (NPC) when the overall treatment time is prolonged. A retrospective study was carried out on 43 advanced NPC (stage Ⅲ and Ⅳ) treated with fractionated High Dose Rate (HDR)–Brachytherapy boost, following external beam radiation therapy and chemotherapy in the period from 2009 to 2015. All patients were irradiated using a cobalt unit and a technique that employed two laterals, opposed fields with a dose of (66 ± 4) Gy. It was followed by HDR –Intra Luminal Radiotherapy after having a gap. The total EQD2 prescribed was (84.75 ± 7) Gy (range, 75–100.5 Gy). The probabilities of disease recurrence within a median follow-up of 24 months (range, 10–78 months) are expected as 0.12, 0.48 and 0.97 (P=0.05) for the overall treatment time of 75, 150 and 250 days respectively. The relative risk of local recurrence of Stage IV NPC patient is about 2.30 times higher than stage Ⅲ patients. The increase of total treatment time may be of different origin resulting in the fall of EQD2. It was observed that the recurrence of disease is significant (P < 0.05) when the overall treatment time is above 100 days where EQD2 lost becomes more than 0.10 Gy/day. The relative risk of disease recurrence of Stage Ⅳ is observed higher than stage Ⅲ nasopharyngeal patients. Keywords: HDR-brachytherapy, advanced NPC, EQD2, overall treatment time
Introduction
Incidence of head and neck cancer is relatively high in north eastern part of India[1–2]. Nasopharyngeal carcinoma (NPC) is observed
JNPC ★ http://www.journalofnasopharyngealcarcinoma.org/
e-ISSN 2312-0398
Published:2016-07-15 ★ DOI:10.15383/jnpc.33
frequently occupying top position amongst the head and neck
Material and Methods
cancers in our hospital. NPC are relatively radiosensitive tumours.
Patient Selection: Forty seven consecutive patients of the advanced
The standard treatment for primary NPC is radical radiotherapy with
NPC (stages Ⅲ–27 patients and Ⅳ–20 patients), who attended the
or without chemotherapy, as surgery is generally not feasible due to
department of Radiotherapy, Regional Cancer Centre, Regional
the peculiar location of the nasopharynx[3–8]. Radiation to
Institute of Medical Sciences, Imphal, India and were treated during
nasopharynx is challenging due to potential injuries to critical
the period from June, 2009 to Sept, 2015, were enrolled in this study.
organs such as optic apparatus, pituitary gland, hypothalamus, spinal
All patients were subjected to the routine diagnostic and metastatic
cord and temporal lobes, which could lead to significant morbidity.
work-up. Four of the patients (2 each for stage Ⅲ and Ⅳ) were
Escalation brachytherapy is commonly used with external beam radiation therapy (EBRT) to locally increase the dose to an area at greatest risk for tumour recurrence, such as the original distribution of gross tumour or the surgical resection site of tumor[9]. In our institute, high dose rate (HDR) brachytherapy is routinely used to boost the dose delivered to the primary NPC site in all locoregionally confined disease treated with intent to cure.
shown relatively long doubling times of tumour volumes (median, 30 days). Studies showed that the prolongation of the overall treatment time resulted in worse outcomes of radiotherapy and doubling time of tumour cells might be reduced during RT to 5 days[10]. Clinical studies on head and neck cancers irradiation have shown the importance of treatment time for local control of disease
.
Radiotherapy
plans
based
on
physical
treatment of 14 months (range 9–21 months) and then excluded from the study. EBRT: All patients (except 4, due to simulator machine problem) were simulated and planned in a customized thermoplastic mask in the supine position. All patients were irradiated using a cobalt unit with bilateral parallel-opposed portals with appropriate shielding.
The clinical observations of the growth of unirradiated cancers have
[10-13]
found developed distant metastasis (in lung and bone) after the
dose
distributions do not necessarily reflect on the biological effects under various irradiation schemes. Traditionally, the biological effective dose (BED) method has been used to assess the biological effectiveness following irradiation of tissues. The linear-quadratic (LQ) model is used by radiologists as a convenient tool to quantify biological effects of radiotherapy[14-16]. Inadequate BED delivery to the treated volume is frequently identified as a possible cause of failure in the radiotherapy of cancers[10-13,17,18]. EQD2 (biologically equivalent dose in 2 Gy fraction) is logistically and conceptually equivalent to BED, but has numerical values which can be directly related to clinical experience as the method converts treatments into isoeffective schedules of 2 Gy fractions[19]. In this study we evaluated the effects of prescribed dose of EQD2 at the standard reference points of treatment for NPC. It is also further discussed
Treatment was delivered as one fraction per day, 5 times a week. The dose was calculated in the mid-plane on the axis of the beam. The total EBRT dose delivered was in the range of 60–70 Gy/30–35 #/6–7 weeks (median dose= 66 Gy). Brachytherapy Application and Treatment Planning: Inflatable balloon nasopharyngeal applicator (Elekta) was used. The applicator was inserted through the ipsilateral nostril depending on the location of the gross disease in the nasopharynx with patient in seated position. About 6 ml of air was pumped inside the hollow plastic tube, which leaded to the nasopharyngeal balloon covering the source transfer tube toward the end expanding to about 3 cm length with 2 cm diameter. Nasal packing was done to avoid any displacement or changes in the geometry of the applicator placement. The position of applicator was confirmed and simulation was done using Simulix Simulator (Elekta). Brachytherapy treatment planning was done using Plato Sunrise Treatment Planning System (Elekta). Dose prescription was done at points 1 cm away from the source for the total treatment length in the range of 3–5 cm (median = 4 cm) using standard source loading pattern without optimization. The median dose delivered with HDR-ILRT was 15 Gy (range: 3–7.5 Gy in 5–2 fractions). The strength of the source (Ir-192) was in the range from 4.081 to 0.347 cGy.m2.h-1.
critically the need to maintain EQD2 for local disease control of the advanced NPC. JNPC ★ http://www.journalofnasopharyngealcarcinoma.org/
e-ISSN 2312-0398
Published:2016-07-15 ★ DOI:10.15383/jnpc.33
Overall Treatment Time: EBRT with concurrent chemotherapy
Where PCF = -[{0.693/ (αTp)}(T+G-Tk)] = proliferation correction
followed by ILRT boost is normally given for advanced stages of
factor, Tp = the potential doubling time of proliferating tumour cells,
NPC.
Tk = kicking off time in proliferation after starting irradiation, T =
The first day of the radiotherapy till the last day of Intra Luminal
treatment time in days and G = gap in days between two treatment
Radiotherapy (ILRT) including all gaps is taken as overall treatment
modalities
time. The relation between the overall treatment times with EQD2 is
respectively[26].The value of α=0.35 Gy-1[24], Tp=13 days[ 26-29], Tk =
discussed critically in this study.
28 days [16, 24] is considered in this study.
Chemotherapy: All of the patients with advanced stages of NPC
The BED is further reported as equivalent dose in 2 Gy per fraction
were treated with 3–4 cycles of Platinum based doublet neoadjuvant
which is termed as EQD2. It is the BED value converted to an
chemotherapy followed by concomitant chemotherapy with low
equivalent dose in traditional 2 Gy fractions:
dose Carboplatin weekly schedule.
of
radiotherapy
or
between
any
one
therapy
BED = EQD2 [1+d/(α/β)]
Clinical Details: Out of 43 patients, 39 patients (Stage Ⅲ–24
or
patients, Stage Ⅳ–15 patients) were found to be having complete
GEC-ESTRO[25] also suggested that, for the whole treatment, total
response; two patient of stage Ⅲ and two patients of stage Ⅳ were
dose values should be reported as physical dose, indicating the
found to be partial responders at the completion of the treatment. The follow up of 6–12 months post treatment showed that four patients of stage Ⅲ and seven patients of stage Ⅳ had local disease seen and detected by imaging modalities. The median follow up of
EQD2 = BED / [1+d/(α/β)]
--- (4)
fractionation and dose rate and in addition as biologically weighted dose (EQD2, biologically equivalent dose in 2 Gy fraction). Statistics：Local disease control was measured from the date of the initiation of radiation therapy to the last follow-up examination. The survival analysis was determined using the Kaplan – Meier survival
patients was 24 months (10–78 months).
method. The statistical significance of observed data was calculated Equivalent Dose in 2 Gy per Fraction, EQD2：Biological effects (E) using the Student’s t-test and Chi-square test, and P
